After binding to specific cell surface receptors, interferon-alpha (IFN-alpha), like other polypeptide hormones and growth factors, is internalized by the cells via receptor-mediated endocytosis. We have been studying the role for internalization of IFN-alpha in responses to IFN-alpha and have found that concanavalin A (Con A) effectively inhibits both the internalization of IFN-alpha and the induction of 2',5' oligo (A) synthetase activity in IFN-treated cells. Similar dose response curves were obtained for the effect of Con A to inhibit IFN internalization and of 2',5' oligo (A) synthetase induction. At least part of the effect of Con A to inhibit the induction of 2',5' oligo (A) synthetase activity was attributable to inhibition of induction of 2',5', oligo (A) synthetase mRNA. The effect of Con A to inhibit protein mobility in the plasma membrane and the correlation between the Con A- mediated inhibition of 2',5' oligo (A) synthetase induction and inhibition of IFN-alpha internalization supports the hypothesis that internalization of IFN receptor complexes and/or receptor mobility may be necessary for some of the responses to IFN- alpha. In studies on the antiproliferative action of IFN-alpha, we have found that glucocorticoids and IFN-alpha synergistically inhibit the growth of some B lymphoblastoid and B lymphoma cell lines. These findings may have clinical relevance in the treatment of certain lymphoid malignancies sensitive to IFN-alpha. In studies on the possible role that the IFN's may play in treatment of AIDS, we have found that IFN-gamma treatment of myelomonocytic cell lines decreases expression of the T4 cell surface protein, which has been implicated to be a receptor for the AIDS virus, HIV-1. This decrease in T4 expression is not due to a generalized loss of cell surface antigens, since several other antigens are either unchanged or increased in IFN-gamma treated cells.